Frontiers in Pharmacology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 7, 2025
Acute
lung
injury
(ALI)
is
a
severe
condition
characterized
by
inflammation,
tissue
damage,
and
persistent
activation
of
the
cyclic
GMP-AMP
(cGAS)-stimulator
interferon
genes
(STING)
pathway,
which
exacerbates
production
pro-inflammatory
mediators
promotes
progression
ALI.
Specific
inhibition
this
pathway
has
been
shown
to
alleviate
ALI
symptoms.
Kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside
(KAE),
an
active
compound
found
in
flowers
Angelica
acutiloba
Kitagawa,
exhibits
anti-inflammatory
antioxidant
properties.
This
study
aimed
investigate
molecular
mechanisms
through
KAE
regulates
cGAS-STING
context
was
induced
using
LPS.
Lung
damage
anti-inflammatory/antioxidant
effects
were
assessed
H&E
staining,
edema
index,
SOD,
MDA,
ELISA
assays.
NO
release
mitochondrial
membrane
potential
(MMP)
measured
JC-1
Griess
methods.
The
impact
on
PANoptosis
analyzed
flow
cytometry,
Western
blot,
immunofluorescence.
significantly
alleviated
lipopolysaccharide-induced
pulmonary
reducing
inflammatory
cell
infiltration,
alleviating
edema,
enhancing
capacity,
decreasing
levels
cytokines
mouse
tissues.
In
both
vitro
vivo
analyses,
downregulated
expression
key
components
including
cGAS,
STING,
p-TBK1,
nuclear
factor-κB.
also
reduced
assembly
PANoptosome,
thereby
attenuating
apoptosis,
necroptosis,
pyroptosis.
Additionally,
inhibited
cGAS
restoring
MMP,
cytosolic
DNA.
improve
inhibiting
DNA
suppressing
activation,
protecting
cells
from
PANoptosis.
Our
findings
provide
valuable
insights
for
development
application
novel
therapeutic
strategies
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
175, С. 116715 - 116715
Опубликована: Май 12, 2024
Ischemic
stroke,
a
devastating
disease
associated
with
high
mortality
and
disability
worldwide,
has
emerged
as
an
urgent
public
health
issue.
A-kinase
anchoring
proteins
(AKAPs)
are
group
of
signal-organizing
molecules
that
compartmentalize
anchor
wide
range
receptors
effector
have
major
role
in
stabilizing
mitochondrial
function
promoting
neurodevelopmental
development
the
central
nervous
system
(CNS).
Growing
evidence
suggests
dysregulation
AKAPs
expression
activity
is
closely
oxidative
stress,
ion
disorder,
dysfunction,
blood-brain
barrier
(BBB)
impairment
ischemic
stroke.
However,
underlying
mechanisms
remain
inadequately
understood.
This
review
provides
comprehensive
overview
composition
structure
protein
(AKAP)
family
members,
emphasizing
their
physiological
functions
CNS.
We
explored
depth
molecular
cellular
AKAP
complexes
pathological
progression
risk
factors
including
hypertension,
hyperglycemia,
lipid
metabolism
disorders,
atrial
fibrillation.
Herein,
we
highlight
potential
pharmacological
target
against
stroke
hope
inspiring
translational
research
innovative
clinical
approaches.
International Journal of Molecular Medicine,
Год журнала:
2024,
Номер
54(3)
Опубликована: Июль 4, 2024
PANoptosis,
a
complex
form
of
proinflammatory
programmed
cell
death,
including
apoptosis,
pyroptosis
and
necroptosis,
has
been
an
emerging
concept
in
recent
years
that
widely
reported
cancer,
infectious
diseases
neurological
disorders.
Cardiovascular
(CVDs)
are
important
global
health
problem,
posing
serious
threat
to
individuals'
lives.
An
increasing
body
research
shows
inflammation
pivotal
role
CVDs,
which
provides
theoretical
basis
for
PANoptosis
promote
the
progression
CVDs.
To
date,
only
sporadic
studies
on
CVDs
have
its
field
not
fully
explored.
Elucidating
various
modes
cardiomyocyte
specific
molecular
mechanisms
links
among
death
under
stressful
stimuli
is
notable
clinical
significance
deeper
understanding
pathophysiology
The
present
review
summarizes
pyroptosis,
necroptosis
their
prospects
Ferroptosis
is
a
unique
form
of
cell
death
that
was
first
described
in
2012
and
plays
significant
role
various
diseases,
including
neurodegenerative
conditions.
It
depends
on
dysregulation
cellular
iron
metabolism,
which
increases
free,
redox-active,
can
trigger
Fenton
reactions,
generating
hydroxyl
radicals
damage
cells
through
oxidative
stress
lipid
peroxidation.
Lipid
peroxides,
resulting
mainly
from
unsaturated
fatty
acids,
by
disrupting
membrane
integrity
propagating
signals.
Moreover,
peroxide
degradation
products
further
affect
components
such
as
DNA,
proteins,
amines.
In
ischemic
stroke,
where
blood
flow
to
the
brain
restricted,
there
increased
absorption,
stress,
compromised
blood-brain
barrier
integrity.
Imbalances
iron-transport
-storage
proteins
increase
oxidation
contribute
neuronal
damage,
thus
pointing
possibility
cells,
especially
neurons,
dying
ferroptosis.
Here,
we
review
evidence
showing
ferroptosis
both
recent
studies
directly
assessing
this
type
death,
well
previous
now
be
revisited
with
our
new
knowledge
mechanisms.
We
also
efforts
made
target
stroke
possible
treatment
mitigate
death.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
174, С. 116428 - 116428
Опубликована: Апрель 9, 2024
Vascular
cognitive
impairment
(VCI)
encompasses
a
range
of
deficits
arising
from
vascular
pathology.
The
pathophysiological
mechanisms
underlying
VCI
remain
incompletely
understood;
however,
chronic
cerebral
hypoperfusion
(CCH)
is
widely
acknowledged
as
principal
pathological
contributor.
Mitochondria,
crucial
for
cellular
energy
production
and
intracellular
signaling,
can
lead
to
numerous
neurological
impairments
when
dysfunctional.
Recent
evidence
indicates
that
mitochondrial
dysfunction—marked
by
oxidative
stress,
disturbed
calcium
homeostasis,
compromised
mitophagy,
anomalies
in
dynamics—plays
pivotal
role
pathogenesis.
This
review
offers
detailed
examination
the
latest
insights
into
dysfunction
within
context,
focusing
on
both
origins
consequences
health.
It
aims
lay
robust
scientific
groundwork
guiding
development
refinement
mitochondrial-targeted
interventions
VCI.
